The long term goal of the project is to more explicity describe the role of the parathyroid glands in calcium homeostasis. The studies are designed to precisely define the control of parathyroid hormone (PTH) secretion during normocalcemia and to determine the manner in which the mechanisms of secretion control may relate to the development of hyperparathyroidism. Experiments will be conducted in normal calves and in calves with experimentally induced secondary hyperparathyroidism. PTH secretion rate will be measured in both groups by collection and radioimmunoassay of parathyroid venous effluent in association with the following conditions: (1) spontaneous variations of plasma calcium concentration in normocalcemic animals; (2) slowly induced alterations of plasma calcium concentration between 9 and 11 milligrams/100 ml; (3) induced hypercalcemia; and (4) induced hypocalcemia. The effect on the parathyroids of substances (e.g., epinephrine, vitamin D metabolites, and calcitonin), which may modulate the response to calcium will be evaluated. These studies should determine the relative importance of calcium and other secretagogues in the control of PTH secretion in normocalcemic animals and may provide insight as to mechanisms involved in the development of parathyroid hyperactivity. More convenient indices of parathyroid secretory activity would accelerate progress of basic research and aid diagnosis of related diseases in man. Studies intended to clarify the relation between plasma immunoreactive PTH concentration and secretory rate will be conducted. The rate of distribution of PTH within the extracellular pool and its metabolic degradation after secretion will be investigated by intravenous administration of both nonlabeled and radioiodinated PTH. The molecular nature of the hormonal material in samples of plasma and lymph, collected following injection of nonlabeled PTH, will be assessed by gel filtration analysis and immunochemical techniques. The conversion of radiolabeled PTH to peptide fragments will be assessed using a microsequencing technique. Parathyroid secretory protein, proPTH, and the proPTH hexapeptide will be evaluated as possible indices of parathyroid activity.